title: Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor.
abstract: Repeated administration of abuse drugs such as morphine elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect plastic changes requiring regulation of glutamatergic system in the brain. In this study, we investigated the effect of morphine sensitization on extracellular glutamate concentration in the hippocampus, a brain region rich in glutamatergic neurons. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular glutamate concentration in the CA1 was decreased following administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular glutamate concentration in this area. The enhancement of glutamate in morphine sensitized rats was prevented by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine sensitization and it is postulated that opioid receptors may play an important role in this effect.
authors.affiliation: Department of Physiology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahmandfar
authors.forename: Seyed Morteza
authors.initials: SM
authors.lastname: Karimian
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
authors.forename: Hossein
authors.initials: H
authors.lastname: Afrouzi
authors.forename: Nasser
authors.initials: N
authors.lastname: Naghdi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D018698:Glutamic Acid; D009020:Morphine